RESUMEN
<p><b>BACKGROUND</b>Paroxysmal kinesigenic dyskinesia (PKD) is the most common subtype of paroxysmal dyskinesias and is caused by mutations in PRRT2 gene. The majority of familial PKD was identified to harbor PRRT2 mutations. However, over two-third of sporadic PKD patients did not carry anyPRRT2 mutation, suggesting an existence of additional genetic mutations or possible misdiagnosis due to clinical overlap.</p><p><b>METHODS</b>A cohort of 28 Chinese patients clinically diagnosed with sporadic PKD and excluded PRRT2 mutations were recruited. Clinical features were evaluated, and all subjects were screened for MR-1, SLC2A1, and CLCN1 genes, which are the causative genes of paroxysmal nonkinesigenic dyskinesia (PNKD), paroxysmal exertion-induced dyskinesia, and myotonia congenita (MC), respectively. In addition, 200 genetically matched healthy individuals were recruited as controls.</p><p><b>RESULTS</b>A total of 16 genetic variants including 4 in MR-1 gene, 8 in SLC2A1 gene, and 4 in CLCN1 gene were detected. Among them, SLC2A1 c.363G>A mutation was detected in one case, and CLCN1 c.1205C>T mutation was detected in other two cases. Neither of them was found in 200 controls as well as 1000 Genomes database and ExAC database. Both mutations were predicted to be pathogenic by SIFT and PolyPhen2. The SLC2A1 c.363G>A mutation was novel.</p><p><b>CONCLUSIONS</b>The phenotypic overlap may lead to the difficulty in distinguishing PKD from PNKD and MC. For those PRRT2- negative PKD cases, screening of SLC2A1 and CLCN1 genes are useful in confirming the diagnosis.</p>
Asunto(s)
Adolescente , Adulto , Niño , Femenino , Humanos , Masculino , Canales de Cloruro , Genética , Corea , Genética , Distonía , Diagnóstico , Genética , Transportador de Glucosa de Tipo 1 , Genética , Proteínas de la Membrana , Genética , Proteínas Musculares , Genética , Mutación , Miotonía Congénita , Genética , Proteínas del Tejido Nervioso , GenéticaRESUMEN
OBJECTIVE@#To explore the effects of exogenous transforming growth factor-beta 1 (TGFbeta1) on peripheral nerve regeneration after the peripheral nerve injury and if TGFbeta1 regulates the expression of basic fibroblast growth factor (bFGF) in the anterior horn motoneurons of spinal cord during regeneration.@*METHODS@#Forty-eight rats were crushed on the right sciatic nerve and then randomly divided into 2 groups: TGFbeta1 group and NS group. In TGFbeta1 group, TGFbeta1 50 microL (0.1 microg/mL) was injected into the proximal nerve near to the crushed nerve and after the operation the injured leg was injected with equal TGFbeta1 whereas the NS was replaced in the NS group. The rats of each group survived for 3, 7, 14 and 21 days after the lesion. The bFGF expression in the anterior horn motoneurons of spinal cord was detected by immunohistochemistry (IHC). Semi-thin section and Fast Blue retrograde tracing were also performed with the rats surviving for 21 days to observe the regeneration of distal end in the injured right sciatic nerve.@*RESULTS@#The number of bFGF immunoreactive positive motoneurons in TGFbeta1 group was obviously higher than that of the NS group (P < 0.05). In the distal sciatic nerve of the rats treated with TGFbeta1, the number and diameter of regenerating myelinated axons and the thickness of myelinated sheath were more than those of the NS group (P < 0.05). The number of motoneurons in spinal cord and neurons in dorsol root ganglia (DRG) labelled with Fast Blue in the NS group was obviously lower than in the TGFbeta1 group (P < 0.01).@*CONCLUSION@#Exogenous TGFbeta1 plays an important role in promoting the peripheral nerve regeneration; TGFbeta1 up-regulates the bFGF expression in the anterior horn motoneurons of spinal cord during the peripheral nerve regeneration.